The epidemic scale and serious complications make atrial fibrillation a major threat to cardiovascular health. In addition to vitamin K antagonists, four new oral anticoagulants (NOAKs) are available for stroke prevention.
Among seniors over 80 years of age, more than one in ten are affected, whereas among those under 50 years of age, fewer than one in 200 have atrial fibrillation [1]. In addition to vitamin K antagonists, four new oral anticoagulants (NOAKs) are available for stroke prevention (apixaban, dabigatran, edoxaban, rivaroxaban). Men with one or more and women with two or more stroke risk factors (CHA2DS2-VASc= heart failure, hypertension, age ≥75 [doppelt], diabetes, stroke, or transient ischemic attack [doppelt], vascular disease, age 65-74, sex [weiblich]) benefit from oral anticoagulation, said Prof. Paulus Kirchhof, MD, Birmingham, UK. No antithrombotic therapy is needed by patients at low risk of stroke. Antiplatelet agents cannot prevent stroke in patients with atrial fibrillation. Influences contributing to thrombus formation in patients with atrial fibrillation include blood stasis in the atria, expression of prothrombotic factors on the atrial endothelium, and systemic coagulation activation [1].
NOAK prefer
Current European guidelines recommend favoring NOAKs over vitamin K antagonists where feasible [2]. Clinical trials have shown reductions in ischemic and hemorrhagic stroke, myocardial infarction, and all-cause mortality compared with warfarin, reported Prof. Christoph Bode, MD, Freiburg, Germany. A comparison of the different NOAKs is difficult, he said, because no direct comparative studies are available. It is likely that the differences are minor, he said. In practice, he said, it is appropriate for physicians to use one or two NOAKs that they know well in all patients and to gain experience with them. It is important to follow the criteria for NOAK dose reduction evaluated in clinical trials, with renal function, age, and weight playing a role, he said. Adherence was better when a once-daily NOAK (edoxaban, rivaroxaban) was prescribed than a twice-daily NOAK (apixaban, dabigatran). In a real-world study (retrospective analysis of a treatment database), adherence was significantly less likely to be suboptimal with once-daily NOAK use (27.2% of patients) than with twice-daily use (32.1%) [3]. In patients with suboptimal adherence, the risk of ischemic stroke was increased by 50%, regardless of the dosing regimen. The availability of an antidote may also play a role in NOAK selection.
Immediate NOAK neutralization for emergencies.
The need for anticoagulation with a NOAK to be lifted as quickly as possible by an antidote is not frequent but unpredictable, said Prof. Charles Pollack, MD, Philadelphia, USA. He led the REVERSE-AD study, the final results of which were recently published [4]. Patients with atrial fibrillation and long-term anticoagulation are usually seniors with multiple comorbidities. If anticoagulation needs to be lifted immediately after an accident (e.g., fall, car accident with polytrauma) or before an emergency intervention, a NOAK antidote is needed that specifically targets only the corresponding NOAK, is easy to use, acts immediately, completely lifts anticoagulation, but does not have a coagulation-enhancing effect. The antidote is not a hemostatic agent, but an agent that eliminates the NOAK effect, Prof. Pollack emphasized. Currently, a specific neutralizing agent is only available for the NOAK dabigatran. The monoclonal antibody fragment idarucizumab binds both free and thrombin-bound dabigatran and abolishes its anticoagulant effect. The antidote is administered as an intravenous infusion, begins to act immediately, and has a short half-life.
In the prospective open-label REVERSE AD trial, 503 patients (95% for stroke prevention in atrial fibrillation) anticoagulated with dabigatran in 173 hospitals (from 39 countries) received the antidote because immediate neutralization of the dabigatran effect was required due to life-threatening emergency situations [4]. Uncontrollable major bleeding was present in 301 patients, and emergency intervention was required in 202 patients (without bleeding), which appeared too risky without NOAK neutralization. This was either an emergency operation (e.g., for acute abdomen, aneurysm, femur fracture, open extremity fracture) or a procedure such as pacemaker implantation. All patients received the fixed dose of 2.5 g idarucizumab intravenously twice, regardless of weight, sex, and renal function. In both patient groups, there was immediate, complete neutralization of the anticoagulant activity of dabigatran. Because of the antidote’s short half-life, dabigatran can be reused after only 24 hours, the speaker said.
Patient-centered management of atrial fibrillation.
Dr. Jeroen Hendriks, Sittard, the Netherlands, spoke about the importance of patient-centered care in atrial fibrillation. Patients with good knowledge of their disease take stroke risk more seriously and want to be actively involved in decisions regarding anticoagulation. Physicians should pay particular attention to patient compliance during the first 90 days because there is a particularly high risk of interruptions in anticoagulation during this period, the speaker said. The ESC has developed two freely available apps (in English) based on the ESC guidelines that support both the physician (AF Manager) and the patient (My AF) [5]. Patients receive information about atrial fibrillation in the app and can save their readings and forward them to their doctor.
Primary prophylaxis of atrial fibrillation
Hypertension is an important risk factor for atrial fibrillation. In hypertensive patients, the incidence of AF is 1-2% per year in clinical trials, reported Dr. Harry Crijns, Maastricht, the Netherlands. Prevention of atrial fibrillation would depend mainly on the blood pressure achieved and not on the type of antihypertensive used. Too aggressive blood pressure reduction, however, is counterproductive and increases the risk of atrial fibrillation. Obesity and obstructive sleep apnea are other important risk factors. Weight-control efforts are probably useful in counteracting the increasing incidence of atrial fibrillation, said Francisco Marín, MD, Murcia, Spain. It is not clear at this time whether CPAP therapy is effective in preventing the development of atrial fibrillation, he said. To increase treatment success, he said, it is also important after ablations to therapeutically influence obesity, hypertension, and sleep apnea. It is likely that regular physical activity of moderate intensity can reduce the risk of AF in the general population, said Laurent Fauchier, MD, Tours, France. In contrast, intense, prolonged endurance exercise could increase the risk of atrial fibrillation 3- to 5-fold in middle-aged men (e.g., marathon runners), but without significantly affecting stroke risk and mortality. Functional and morphological atrial changes are probably responsible for the increased risk of atrial fibrillation.
Literature:
- Kirchhof P: The future of atrial fibrillation management: integrated care and stratified therapy. Lancet 2017 (Epub ahead of print).
- Kirchhof P, et al: ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37: 2893-2962.
- Alberts MJ, et al: Association between once- and twice-daily direct oral anticoagulant adherence in nonvalvular atrial fibrillation patients and rates of ischemic stroke. Int J Cardol 2016; 215: 11-13.
- Pollack CV, et al: Idarucizumab for dabigatran reversal – full cohort analysis. N Engl J Med 2017; 377: 431-441.
- www.escardio.org/AF-apps
CARDIOVASC 2017; 16(5): 39-40